Dysmorphogenesis of kidney cortical peritubular capillaries in angiopoietin-2-deficient mice

Am J Pathol. 2004 Dec;165(6):1895-906. doi: 10.1016/S0002-9440(10)63242-7.


Angiopoietin-2 (Ang-2) modulates Tie-2 receptor activation. In mouse kidney maturation, Ang-2 is expressed in arteries, with lower levels in tubules, whereas Tie-2 is expressed by endothelia. We hypothesized that Ang-2 deficiency disrupts kidney vessel patterning. The normal renal cortical peritubular space contains fenestrated capillaries, which have few pericytes; they receive water and solutes which proximal tubules reclaim from the glomerular filtrate. In wild-type neonates, alpha smooth muscle actin (alpha SMA), platelet-derived growth factor receptor beta (PDGFR beta), and desmin-expressing cells were not prominent in this compartment. In Ang-2 null mutants, alpha SMA, desmin, and PDGFR beta prominently immunolocalized in cortical peritubular locations. Some alpha SMA-positive cells were closely associated with CD31- and Tie-2-positive peritubular capillary endothelia, and some of the alpha SMA-positive cells expressed PDGFR beta, desmin, and neural/glial cell 2 (NG2), consistent with a pericyte-like identity. Immunoblotting suggested an increase of total and tyrosine-phosphorylated Tie-2 proteins in null mutant versus wild-type kidneys, and electron microscopy confirmed disorganized capillaries and adjacent cells in cortical peritubular spaces in mutant neonate kidneys. Hence, Ang-2 deficiency causes dysmorphogenesis of cortical peritubular capillaries, with adjacent cells expressing pericyte-like markers; we speculate the latter effect is caused by disturbed paracrine signaling between endothelial and surrounding mesenchymal precursor cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-2 / deficiency*
  • Animals
  • Capillaries / abnormalities*
  • Desmin / metabolism
  • Kidney Cortex / blood supply*
  • Mice
  • Mice, Knockout
  • Morphogenesis
  • Muscle, Smooth / metabolism
  • Pericytes / metabolism
  • Pericytes / pathology
  • Phosphorylation
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Receptor, TIE-2 / metabolism
  • Renal Circulation
  • Tyrosine / metabolism


  • Angiopoietin-2
  • Desmin
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Tyrosine
  • Receptor, Platelet-Derived Growth Factor beta
  • Receptor, TIE-2